Method for restoring gait in individuals with chronic spinal cord injury

ABSTRACT

A method for restoring functional ambulation in subjects with incomplete spinal cord injuries which includes partial weight bearing therapy followed by epidural spinal cord stimulation (ESCS) to facilitate partial weight bearing therapy and over-ground walking. Electrical epidural stimulation (EES) is generated by an implanted device during partial weight bearing therapy on a treadmill. The subject is then transitioned to full weight bearing gait training on a treadmill with EES to over-ground gait training with EES and a walker, and finally to full weight bearing independent stepping over-ground with EES with or without an assistive device.

CROSS-REFERENCE TO RELATED APPLICATION

[0001] This application claims the benefit of, and priority to, U.S.provisional application Serial No. 60/261,055, filed Jan. 11, 2001,which application is hereby incorporated by reference in its entirety.

FIELD OF INVENTION

[0002] The present invention generally relates to a method for restoringgait in individuals having spinal cord injuries. More particularly, thepresent invention relates to a method for restoring functionalambulation in individuals having incomplete spinal cord injuries whichincludes partial weight bearing therapy followed by epidural spinal cordstimulation to facilitate partial weight bearing therapy and over-groundwalking.

BACKGROUND OF THE INVENTION

[0003] Among the approximately 250,000 spinal cord injured (SCI) in theUnited States, there is a considerable population of chronic incompletespinal cord injuries (ISCI) who are designated as ASIA B (some sensorysparing and abolished motor power) or C (some sensory sparing andsub-functional motor power) in the lower extremities. Generally, theyare wheelchair-dependent, although they may be able to stand or eventake a few crude steps for exercise, but are not consistent functionalambulators at home or within the community.

[0004] Two novel strategies have been individually employed to augmentlocomotion rhythm generation, making use of the adaptability andcapacity for retraining/learning of spinal cord circuits: partial weightbearing therapy (PWBT) and epidural spinal cord stimulation (ESCS). PWBThas evolved from observations of chronic spinal animals, whereby movinga treadmill can initiate and sustain locomotion when the body issupported. (See Muir GD, Steeves JD, “Sensorimotor Stimulation toImprove Locomotor Recovery After Spinal Cord Injury”, TINS 1997, volume20, pages 72-77.) As a consequence, various afferent inputs into theintrinsic spinal circuitry contribute to a coordinated locomotionpattern with state-dependent and phase-dependent reflexes. It is wellrespected that PWBT facilitates functional walking among chronic ASIA D(significant functional motor power) patients. To our knowledge, thereare no publications documenting the effect of PWBT among ASIA B and ASIAC patients with regard to transitioning treadmill walking to restorationof functional ambulation in terms of household or community walking.

[0005] Non-patterned ESCS, which modulates segmental spinal and/or brainstem-spinal pathways in the ISCI, has also shown potential in initiatingand sustaining locomotion among Multiple Sclerosis and ASIA D patients.ESCS at the lumbar enlargement in animals, with low frequency, longpulse duration, and supramotor threshold current intensity, induceshind-limb locomotion patterns following an acute mid-thoracic spinalcord transection. (See Iwahara T, Atsuta Y, Garcia-Rill E, Skinner RD,“Spinal Cord Stimulation-Induced Locomotion in the Adult Cat”, Brain ResBull 1992, pages 99-105.) These parameters, however, contrast withDimitrijevic's observations in acute human experiments with clinicallycomplete SCI in a supine position. (See Dimitrijevic MR, Gerasimenko Y,Pinter MM, “Evidence for a Spinal Central Pattern Generator in Humans”,Ann N Y Acad Sci 1998; volume 860: pages 360-376.)

SUMMARY OF THE INVENTION

[0006] Given that PWBT or ESCS alone does not induce functional walking,we posited that in a subset of ASIA C patients (i.e., all muscles of thelower extremity are sub-functional), a combination of the two noveltherapies (PWBT and ESCS) would be more effective than either therapyalone in restoring functional walking.

BRIEF DESCRIPTION OF THE DRAWINGS

[0007]FIG. 1: Gas exchange data of the patient walking a similardistance (45 m) under ESCS and non-ESCS conditions during the earlytraining phase.

[0008] Panel A: All values shown are the exercise-induced (net)increases above resting values, which were essentially identical underboth conditions. The values suggest that the energy cost for walkingthis distance is reduced by ˜20% for the ESCS condition.

[0009] Panel B: the respiratory exchange ratio (RER; VCO₂/VO₂) elicitedby activated muscles during walking (net values) during ESCS andnon-ESCS. Under conditions of acid-base balance, the RER is equal to therespiratory quotient (RQ). The entire physiological range of RQ is 0.70(all fat oxidation) to 1.00 (all carbohydrate oxidation). Assumingacid-base balance (see text), the RQ for ESCS indicated that fatprovided ˜30% and carbohydrate ˜70% of the energy, whereas the RQ fornon-ESCS suggested that virtually 100% of the energy was derived fromcarbohydrate. Thus, an 8-fold increase in fat oxidation occurred withESCS.

[0010]FIG. 2: Duration of time for the subject to traverse a distance of17 m at different stages of the treatment. Walking speed increasedduring PWBT treatment, but the patient remained dysfunctional. Thus,ESCS was associated with an immediate increase in walking speed. Thedifference in performance converged after four months of training.

DETAILED DESCRIPTION

[0011] Methods

[0012] The Institutional Review Board of the two institutions approvedthe study and written informed consent was obtained from the subject. A43-year-old male subject with C5-6 ISCI (ASIA C) quadriplegia (3.5 yearspost injury) was recruited. PWBT was performed using the LiteGait™system (Mobility Research, Tempe, Ariz.). Under the guidance of physicaltherapists, the subject underwent progressive training with increasingtreadmill rates and degree of weight bearing until he demonstrated aplateau in performance.

[0013] A pair of Pisces-Quadplus electrodes (in combination with theX-TREL stimulation system by Medtronic Inc., Minneapolis, Minn.) wereinserted into the dorsal epidural space over the upper lumbarenlargement of the spinal cord. After surgical wound healing andretraining with PWBT to pre-surgery levels, a variety of electricalparameter sets were examined to test the efficacy of ESCS to enhancelocomotion performance. Locomotion characteristics were analyzed bymeasuring average speed, stepping symmetry, swing/stance times, sense ofeffort (approximating the Borg Scale), physical work capacity, and wholebody metabolic activity.

[0014] Results

[0015] PWBT led to an improved stereotypic stepping pattern on thetreadmill and during an over-ground 15 m walk with extremely low speed,poor endurance, and a marked sense of effort (8/10). After combiningPWBT and ESCS, immediate improvements were noted: a propensity toexhibit a smoother, more organized stepping pattern at higher treadmillrates and self-supported body weight, considerable improvement inendurance and speed during over-ground walking, and decreased sense ofeffort (2/10).

[0016] Vital ESCS parameters included electrode distance, pulseduration, and amplitude. We observed that long pulse durations (e.g.,0.8 msec) were essential while frequencies (e.g., 20-60 Hz) werecomparatively less sensitive. The amplitude was above sensory threshold(sense of “parasthesia or vibration”) but below that causing motorcontraction. The electrode distance was at least 15 mm to cover a widesegment of the spinal cord lumbar enlargement.

[0017] Early in the transition from PWBT to over-ground walking, the gasexchange data revealed that ESCS reduced exercise-induced CO₂ andproduction and O₂ consumption rates (FIG. 1A). The net respiratoryexchange ratio or RER (VCO₂/VO₂) was markedly reduced by ESCS (FIG. 1B).With Non-ESCS walking, RER was 0.99, suggesting that fat provided ˜3% ofthe energy, and carbohydrate (CHO) the remaining ˜97%. With stimulation,the net RER was 0.907, inferring that fat and CHO provided ˜31% and ˜69%of the energy, respectively (FIG. 1).

[0018] ESCS was associated with increased walking speed and decreasedsense of effort by a factor of three. With 1.5 months of continuedtraining, the average walking speed, gas exchange responses, andendurance converged between the two conditions (ESCS and non-ESCS). Thetrend line in FIG. 2 demonstrates a continued improvement for thenon-ESCS condition. After four months of over-ground training, thesubject could ambulate 270 m, which enabled him to perform community andhomebound functional ambulation.

[0019] Discussion

[0020] Purportedly, the mechanism of PWBT has been ascribed to theretraining of the spinal cord circuits to promote the sensitivity of thesystem to generate locomotion rhythm-related signals, within the contextof both motor drives and sensory reflexes. When the injury is severe(ASIA B and C), signals from motor drives and sensors are week. Hence,the success of PWBT to promote functional ambulation is difficult toachieve but capable of eliciting a semblance of “use-dependent” behaviorduring over-ground walking. We theorize that when ESCS is applied inconjunction with PWBT, the electrical current provides themodulation/amplification of neural circuits responsible for locomotionrhythm generation by further exciting segmental afferent inputs andfacilitating a “stored” locomotion program.

[0021] The gas exchange data indicated that ESCS reduced the O₂ andenergy cost of walking by ˜20%. The impact of ESCS on CO₂ production wasmore pronounced. If acid-base balance during walking is assumed, gasexchange data revealed an 8-fold-greater exercise-induced fat oxidationrate with ESCS (FIG. 1). Alternatively, lower CO₂ production duringESCS-assisted walking reflected less accumulation of blood lactate andassociated bicarbonate titration. Both interpretations imply that ESCSreduced the dependence of exercising muscle on glycolysis, and henceaccounted for the marked improvement in muscle endurance observed in theESCS condition. We conclude that ESCS may elicit greater activation ofan oxidative motor unit pool in the spinal cord via modulating largeafferent input (e.g., la fibers) which can alter motor unit recruitmentpattern (see Burke RE, Edgerton VR, “Motor Unit Properties and SelectiveInvolvement in Movement”, Exerc Sport Sci Rev 1975, volume 3, pages31-81), thereby reducing the sense of effort (see Granit R, “ConstantErrors in the Execution and Appreciation of Movement”, Brain 1972,volume 95, pages 649-660) and the energetic cost of walking andexpanding physical work capacity.

[0022] We propose that ESCS augmented the “use-dependent plasticity”created by PWBT and concur with the view that ESCS “has the potentialfor serving as a valuable adjunct to post-SCI treadmill training andother therapeutic interventions” (see “Spinal Cord Stimulation-InducedLocomotion in the Adult Cat”, id.) Although the results reported hereare derived from only one subject, it is clear that the combined PWBTand ESCS therapy can facilitate restoration of functional ambulation ofa wheelchair-dependent ISCI patient. Further trials of this therapy needto be tested in more ASIA B and ASIA C patients.

[0023] Acknowledgement

[0024] We gratefully acknowledge the support of the Good SamaritanRegional Medical Center and the Arizona State University. We alsorecognize the assistance of the physical therapy staff at the GoodSamaritan Regional Medical Center, Qingjun Wang, Dr. Gary Yamaguchi, Dr.James Sweeney and Jeffrey Thrasher, to this project. We appreciate Dr.Amir Seif for his valuable insight in the project, Medtronic, Inc. forcontributing the stimulation systems, and partial funding from theWhitaker Foundation.

1. A method for restoring functional ambulation in subjects havingincomplete spinal cord injuries comprising the steps of: a. Providingpartial weight bearing therapy until a subject reaches a plateau inlocomotion rhythm generation; and b. Electrically stimulating the spinalcord with an implanted stimulation device.
 2. The method of claim 1wherein the step of providing partial weight bearing therapy furthercomprises the step of achieving partial weight bearing gait performanceon a treadmill with or without one or more therapists moving thesubject's legs.
 3. The method of claim 2 wherein partial weight bearinggait performance includes transition on the treadmill from one weightbearing/treadmill rate level to another.
 4. The method of claim 3wherein the subject is transitioned across a number of therapeuticlevels upon meeting a predetermined set of criteria.
 5. The method ofclaim 4 wherein the predetermined set of criteria include an alternatinggait with no more than 50% asymmetry, no assistance by a therapist for 3sixty second periods on the same day for three consecutive days, and abreakdown of the gait performance criteria at a higher weight/treadmillrate condition.
 6. The method of claim 2 wherein partial weight bearinggait performance includes final gait performance which determineseligibility for stimulation.
 7. The method of claim 6 wherein final gaitperformance is determined at a specific degree of weight bearing andtreadmill rate that continually produces breakdown of the gait over afour week period.
 8. The method of claim 1 wherein the step ofelectrically stimulating the spinal cord includes the steps of: a.Surgically implanting a spinal cord stimulating device in the subject;and b. providing gait training with electrical epidural stimulationgenerated by the stimulating device.
 9. The method of claim 8 whereinthe step of providing gait training with electrical epidural stimulationcomprises the steps of: a. providing partial weight bearing gaittraining on a treadmill with electrical epidural stimulation (EES) toinvestigate stimulus patterns; b. transitioning from partial weightbearing gait training on a treadmill with EES to full weight bearinggait training on a treadmill with EES and over ground with EES with awalker to further refine stimulus patterns; and c. achieving full weightbearing independent stepping over ground without a harness with EES. 10.The method of claim 9 wherein the step of achieving full weight bearingindependent stepping is done with or without an assistive device.